Effect of Interleukin-12 on the Expression of E-selectin in Mouse Model of Lewis Lung Carcinoma

Lee, Sang Haak; Shin, Yoon; Yoon, Hyoung Kyu; Lee, Sook Young; Kim, Seok Chan; Kweon, Soon Seok; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak

Abstract

BACKGROUND: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-alpha, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules.
METHODS
Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-alpha, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin.
RESULTS
In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were observed in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-alpha increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues.
CONCLUSIONS
These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may play a role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-alpha may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.